Anxiety is an important regulator of alcohol consumption and addiction. In agreement, neuropeptide systems that modulate anxiety have been shown to play a role in the regulation of alcohol-related behaviors. Among these may be the corticotropin-releasing factor (CRF) type 2 receptor (CRF2 receptor)-activating urocortin (Ucn) peptide system. The goal of the present proposal is to characterize the role of the urocortinergic neuropeptide system in the context of alcohol administration. First, the effect of CRF receptor ligands microinjected into the CRF2 receptor-rich lateral septal nuclei (LS) on alcohol consumption will be investigated. Second, the neuroanatomical difference in the Ucn system between alcohol-preferring and non-preferring strains of mice will be investigated with retrograde neuronal tracing. Third, the regulation by alcohol exposure of the CRF2 receptor levels in the LS will be assayed with receptor autoradiography. It is hypothesized that alcohol consumption will regulate, and be regulated, by CRF2R activity in the LS. It is additionally hypothesized that mice that prefer alcohol will contain stronger Ucn projections to the LS than non-preferring mice. Findings of this proposal will provide an important contribution to work highlighting the importance of stress- and anxiety-modulating neuropeptide systems in the regulation of alcohol-related behaviors.